Common artificial sweeteners linked to cognitive decline in large study

A new study published in the journal Neurology provides evidence that regular consumption of certain artificial and low-calorie sweeteners may be linked to a faster decline in memory and other cognitive abilities over time. Using data from more than 12,000 middle-aged and older adults in Brazil, researchers found that individuals who consumed higher amounts of these sweeteners tended to show steeper drops in verbal fluency, memory, and overall cognitive function over an eight-year period. The association appeared stronger in people with diabetes but was also observed among participants without the condition.

With global dementia cases projected to triple by 2050, researchers are increasingly focused on identifying lifestyle factors that might influence cognitive aging. While sugary diets have been linked to poorer brain health, many individuals have shifted toward low- and no-calorie sweeteners as perceived healthier alternatives. These sweeteners—commonly found in diet beverages, yogurts, protein bars, and tabletop products—include aspartame, saccharin, acesulfame potassium, and sugar alcohols like erythritol and xylitol.

Despite their widespread use, concerns have grown around their potential health effects. Prior studies have linked artificial sweeteners to higher risks of diabetes, cardiovascular problems, and depression, even when consumed within official safety limits. Some research has also suggested a potential connection between these sweeteners and dementia or poor memory, but evidence from large-scale, long-term studies has been lacking. The current study was designed to address this gap.

The research drew on data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a multicenter cohort that began in 2008 and enrolled over 15,000 public employees aged 35 and older from six cities across Brazil. After excluding individuals with incomplete dietary data or extreme reported calorie intake, the final sample included 12,772 adults, with an average age of 52 at baseline. Participants were followed over three waves of assessment: 2008–2010, 2012–2014, and 2017–2019—a span of approximately eight years.

At the start of the study, participants completed a detailed food frequency questionnaire that asked about their diet over the past year. This allowed researchers to estimate the intake of seven specific low- and no-calorie sweeteners: aspartame, saccharin, acesulfame potassium, erythritol, xylitol, sorbitol, and tagatose.

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Based on total daily intake, participants were divided into three consumption groups. The lowest group averaged 20 milligrams per day, while the highest group averaged 191 milligrams per day—an amount equivalent to the aspartame content of one can of diet soda. Among all sweeteners, sorbitol was consumed in the highest quantity, with an average intake of 64 milligrams per day.

Cognitive performance was assessed at the start, middle, and end of the follow-up period. The battery of tests included measures of verbal fluency, working memory, word recall, and processing speed, enabling researchers to track changes in memory, language, and general thinking skills. These scores were standardized to allow comparison across waves and participants.

After statistically adjusting for a wide range of factors—including age, sex, income, physical activity, blood pressure, cardiovascular disease, body mass index, and diet quality—the researchers found that individuals in the highest tertile of sweetener consumption showed a 62% faster decline in global cognitive scores than those in the lowest group. This translated to an estimated 1.6 additional years of cognitive aging over the eight-year period. Participants in the middle group experienced a 35% faster decline, equivalent to about 1.3 extra years of aging.

The association between sweetener intake and cognitive decline was strongest in adults under the age of 60. In this group, higher consumption was linked to steeper losses in verbal fluency and overall cognition. Among those aged 60 and older, the study did not find a significant association between sweetener intake and cognitive performance. The researchers also found that the relationship between sweetener use and cognitive decline was stronger in individuals with diabetes compared to those without.

When each sweetener was analyzed separately, consumption of aspartame, saccharin, acesulfame potassium, erythritol, xylitol, and sorbitol was associated with faster decline in global cognition, especially in memory and verbal fluency. In contrast, tagatose—a naturally occurring sugar found in some dairy products and fruits—was not associated with cognitive decline.

Notably, the trend held even when looking at the frequency of consumption, rather than the exact quantity. Participants who consumed any type of low- or no-calorie sweetener on a daily basis showed a significantly faster decline in memory, language, and overall cognitive function compared to those who consumed sweeteners only occasionally or not at all.

“Low- and no-calorie sweeteners are often seen as a healthy alternative to sugar, however our findings suggest certain sweeteners may have negative effects on brain health over time,” explained Claudia Kimie Suemoto of the University of São Paulo, the senior author of the study.

Although the study was large and followed participants over several years, the researchers caution against drawing firm conclusions about cause and effect. The study relied on self-reported dietary data collected only at the beginning of the study, which may not capture long-term changes in diet. People with certain health conditions, such as diabetes or obesity, may also be more likely to consume artificial sweeteners in place of sugar, raising the possibility that underlying health issues, rather than the sweeteners themselves, contributed to cognitive decline.

In addition, while the researchers adjusted for a wide range of demographic, clinical, and lifestyle factors, unmeasured variables could still play a role. The study also lacked brain imaging or biological markers that could offer clues about how these sweeteners might affect brain structure or function.

Despite these caveats, the new findings add to a growing body of research raising concerns about the long-term safety of common sugar substitutes. Recent laboratory studies have suggested that erythritol, a sugar alcohol frequently used in low-carbohydrate and ketogenic products, may impair the function of blood vessels in the brain. In one in vitro study, erythritol increased oxidative stress and reduced nitric oxide production in human endothelial cells, potentially disrupting blood flow and increasing the risk of stroke.

Epidemiological studies have also linked elevated levels of erythritol in the blood to higher risks of heart attacks and strokes, while clinical trials have reported increased platelet reactivity following erythritol intake—another possible contributor to clot formation.

Sucralose, another widely used sweetener, has been implicated in altered brain activity related to hunger and reward. A recent brain imaging study found that sucralose increased activity in the hypothalamus, a region involved in appetite regulation, and heightened connectivity with brain areas involved in motivation and sensory processing. These effects varied depending on sex and body weight, with women and individuals with obesity showing stronger responses. Such findings suggest that sucralose may disrupt the brain’s normal signaling related to satiety, potentially contributing to overeating or altered eating behavior over time.

While these studies do not focus directly on cognition, they raise broader concerns about how artificial sweeteners may influence brain health through vascular, metabolic, and neural pathways—concerns that align with the new findings from Brazil.

In an accompanying editorial published in Neurology, Rush University physician scientist Thomas M. Holland wrote that these findings pose “a fundamental question” to the medical community. “In our efforts to prevent stroke and preserve cognition through dietary modification, are we inadvertently recommending substances that may accelerate the very cognitive decline we seek to prevent?”

The new study, according to Holland, has “provided neurologists, and the broader medical community, caring for cognitively at-risk populations, with critical evidence that dietary counseling must extend beyond traditional cardiovascular risk reduction to address the potential cognitive effects of food additives, particularly artificial sweeteners. Supporting long-term brain health requires a proactive, integrated approach, optimizing diet, movement, sleep, stress, cognitive stimulation, and social connection to build cognitive resilience over time.”

Given the widespread consumption of artificial sweeteners, especially among people seeking to manage weight or blood sugar, researchers emphasize the need for more longitudinal and experimental studies to clarify their potential effects on the brain. Future research should include repeated dietary assessments over time, neuroimaging to detect changes in brain structure, and biomarkers of inflammation and neurotoxicity.

There is also a need to examine whether certain populations—such as people with diabetes, metabolic syndrome, or low insulin sensitivity—are more vulnerable to the potential harms of artificial sweeteners. In addition, researchers should compare the cognitive effects of natural sweeteners like tagatose, stevia, or monk fruit to those of synthetic ones.

“While we found links to cognitive decline for middle-aged people both with and without diabetes, people with diabetes are more likely to use artificial sweeteners as sugar substitutes,” said Suemoto. “More research is needed to confirm our findings and to investigate if other refined sugar alternatives, such as applesauce, honey, maple syrup or coconut sugar, may be effective alternatives.”

The study, “Association Between Consumption of Low- and No-Calorie Artificial Sweeteners and Cognitive Decline: An 8-Year Prospective Study,” was authored by Natalia Gomes Gonçalves, Euridice Martinez-Steele, Paulo A. Lotufo, Isabela Bensenor, Alessandra C. Goulart, Sandhi Maria Barreto, Luana Giatti, Carolina Perim de Faria, Maria del Carmen Bisi Molina, Paulo Caramelli, Dirce Maria Marchioni, and Claudia Kimie Suemoto.